Esters and amides derivatives of (−)-4-Chloro-α-(3-trifluoromethylphenoxy)phenylacetic acid (halofenic acid) are chiral compounds and are useful in ameliorating a variety of physiological conditions, including conditions associated with blood lipid deposition, Type II diabetes and hyperlipidema (see, e.g., U.S. patent application Ser. No. 10/656,567 and U.S. Pat. No. 6,262,118 which are incorporated herein by reference in their entirety). Halofenic acid contains a single chiral center at an asymmetrically substituted carbon atom alpha to the carbonyl carbon atom, and therefore exist in two enantiomeric forms. It has been found that the (−)-enantiomer of halofenic acid is about twenty-fold less active in its ability to inhibit cytochrome P450 2C9 compared to the (+)-enantiomer. Id. Administration of a racemic halofenic acid or its derivatives can lead to a variety of drug interaction problems with other drugs, including anticoagulants, anti-inflammatory agents and other drugs, that are metabolized by this enzyme. Id. It is desirable to administer the (−)-enantiomer of halofenic acid or its derivatives which is substantially free of the (+)-enantiomer to reduce the possibility of drug interactions. Thus, enantiomerically enriched forms of α-(phenoxy)phenylacetic acids or its derivatives are valuable chemical intermediates for the preparation of pharmaceutical compounds.
As shown below, various synthetic routes for making α-(phenoxy)phenylacetic acid derivatives have been reported in literature. Unfortunately, these molecules are often difficult to be produced with high enantiomeric purity and in high yields by known synthetic methods.

As illustrated in Scheme 1, Devine et al. were able to make α-(phenoxy)phenylacetic acids stereoselectively using a pyrrolidine derived lactamide as a chiral auxiliary (see, U.S. Pat. Nos. 5,708,186 and 5,856,519, the teachings of which are incorporated herein by reference). However this method also has several drawbacks including a) multiple isolation steps and b) low isolated yields. Therefore, there is a need for a more efficient process for producing α-(phenoxy)phenylacetic acid stereoselectively as well as derivatives thereof, e.g., (−)-halofenate. Quite surprisingly, the present invention fulfills this and other needs.